New gene mutation reveals new cause of rare neurological diseases

Scientists have discovered a new cause of spastic ataxia, and believe this cause is also a trigger for other mitochondrial diseases – neurological disorders that can lead to serious coordination, growth, visual, speech, and muscle defects.

Researchers at St George’s, University of London have found a gene mutation mechanism that causes a new type of defect in mitochondria – the parts of cells responsible for creating energy from food and oxygen. They made the discovery when they found a new gene that, when mutated by this mechanism, can cause spastic ataxia.

Although disorders resulting from mitochondrial abnormalities are well documented, this particular mutation mechanism – an abnormality the researchers have named ‘maturation defect of mitochondrial ribonucleic acid (RNA)’ – has not been seen before. RNA is the genetic material that transcribes instructions sent by DNA into actions, such as the production of protein in cells, needed for cell development.

The researchers found that the mitochondrial RNA of the affected gene has shortened chains of nucleotides, the molecules that make up RNA and DNA. These incomplete chains – the maturation defect mechanism – can result in the debilitating symptoms of spastic ataxia.

Mitochondrial diseases affect around one in every 11,000 adults, with a further one in 6,000 at risk of developing disease. They can be hard to identify as even diseases belonging to the same sub type can have entirely different symptoms.

Andrew Crosby, professor of medical genetics at St George’s, who led the study, said: “Our findings define a new subclass of mitochondrial dysfunction and disease mechanism. This is an important discovery as there are other neurodegenerative disorders that may be caused by the same mechanism.

“This sheds light on an area of genetic disease that we still don’t know very much about, and could help diagnose other disorders. But a lot more work is needed before any new treatments could be developed.”

The findings of the study have been published in The American Journal of Human Genetics.

Prof Crosby and his team at St George’s are involved in a long-term project investigating genetic disorders among the Amish communities in the USA. The latest study involved genetic analysis of an extended Amish family in which multiple children were affected by spastic ataxia.